Barbiturates Absorption from stomach

Kakemi, K. Arita, T. Hori, R. Konishi, R., Absorption and excretion of drugs. XXX. Absorption of barbituric acid derivatives from rat stomach, Chem. Pharm. Bull. 17, 1534-1539 (1967). 

The rates of oral absorption of benzodiazepines differ depending on a number of factors, including lipophilicity. Oral absorption of triazolam is extremely rapid, and that of diazepam and the active metabolite of clorazepate is more rapid than other commonly used benzodiazepines. Clorazepate is converted to its active form, desmethyldiazepam (nordiazepam), by acid hydrolysis in the stomach. Oxazepam, lorazepam, and temazepam are absorbed from the gut at slower rates than other benzodiazepines. The bioavailability of several benzodiazepines, including chlordiazepoxide and diazepam, may be unreliable after intramuscular injection. Most of the barbiturates and other older sedative-hypnotics are absorbed rapidly into the blood following their oral administration. 

Approximately 50-90% of the long-acting barbiturates are slowly absorbed from the gastrointestinal tract. Absorption is more rapid when ingested on an empty stomach and in the presence of alcohol. The onset of action varies 30-60 min for mephobarbital... 

Consider the three barbituric acid derivatives thiopental, secobarbital, and barbital with respective pKa of 7.6, 7.9, and 7.8. These drugs are very weak acids. On the basis of their ionization constants we would expect very little difference in their absorption rates from the stomach, yet the drugs are absorbed at very different rates. The reason becomes apparent when the partition coefficients between chloroform and water are considered. Thiopental s value is over 100, whereas the values of secobarbital and barbital are 23 and 0.7, respectively. Now which would one predict to be the least rapidly absorbed and which the most By considering only one physicochemical parameter and excluding others, erroneous conclusions can result. Figure 1-2 illustrates a hypothetical relationship of biological activity as a function of pH only. 

ABSORPTION, FATE, AND EXCRETION For sedative-hypnotic use, the barbiturates usually are administered orally (Table 16-3) absorption is rapid and nearly complete. The onset of action varies from 10-60 minutes, depending on the agent and the formulation, and is delayed by the presence of food in the stomach. When necessary, intramuscular injections of solutions of the sodium salts should be placed deeply into large muscles to avoid the pain and possible necrosis that can result at more superficial sites. The intravenous route usually is reserved for the management of status epilepticus (phenobarbital sodium) or for the induction and/or maintenance of general anesthesia (e.g., thiopental or methohexital). 

Eirst aid treatment for humans accidentally poisoned with 1080 includes irmnediate emesis and gastric lavage followed by an oral dose of magnesium sulfate or sodium sulfate to remove the poison from the alimentary tract before absorption of lethal quantities can occur. When the stomach is emptied, oral administration of ethanol may be beneficial. The patient should be put at complete rest and given barbiturates having moderate duration of action, such as sodium amytol, to... 

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